Methyl Salicylate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₈H₈O₃ 152.15

Benzoic acid, 2-hydroxy-, methyl ester;

Methyl Salicylate CAS RN^®: 119-36-8.

1 DEFINITION

Methyl Salicylate is produced synthetically or is obtained by maceration and subsequent distillation with steam from the leaves of Gaultheria procumbens L. (Fam. Ericaceae) or from the bark of Betula lenta L. (Fam. Betulaceae). It contains NLT 98.0% and NMT 102.0% of methyl salicylate (C₈H₈O₃).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197F

B. CHROMATOGRAPHIC IDENTITY

Analysis: Proceed as directed in the Assay.

Acceptance criteria: The retention time of the major peak of the Sample solution corresponds to that of the Standard solution.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol and 0.1% phosphoric acid (55:45)

Diluent: Methanol

System suitability solution: 150 µg/mL of USP Methyl Salicylate RS and 3 µg/mL of USP Methyl Salicylate Related Compound A RS in Diluent

Standard solution: 150 µg/mL of USP Methyl

Sample solution: 150 µg/mL of Methyl

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm

Column: 4.6-mm × 7.5-cm; 3.5-µm packing L7

Column temperature: Ambient

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: 7 min

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for methyl salicylate and dimethyl 4-hydroxyisophthalate are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.5 between the methyl salicylate and dimethyl 4-hydroxyisophthalate peaks, System suitability solution

Tailing factor: NMT 1.5 for the methyl salicylate peak, Standard solution

Relative standard deviation: NMT 0.5% for the methyl salicylate peak, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methyl salicylate (C₈H₈O₃) in the portion of Methyl Salicylate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Methyl Salicylate RS in the Standard solution (µg/mL)

C_U = concentration of Methyl Salicylate in the Sample solution (µg/mL)

Acceptance criteria: 98.0%-102.0%

4 IMPURITIES

LIMIT OF SALICYLIC ACID AND DIMETHYL 4-HYDROXYISOPHTHALATE

Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.15 µg/mL of USP Salicylic Acid RS, 0.15 µg/mL of USP Methyl Salicylate RS, and 0.75 µg/mL of USP Methyl Salicylate Related Compound A RS in Diluent

System suitability

Sample: Standard solution

[NOTE-The relative retention times for salicylic acid, methyl salicylate, and dimethyl 4-hydroxyisophthalate are 0.6, 1.0, and 1.2, respectively.]

Suitability requirements

Resolution: NLT 4 between the salicylic acid and methyl salicylate peaks; NLT 2 between the methyl salicylate and dimethyl 4-hydroxyisophthalate peaks

Relative standard deviation: NMT 3% for all three peaks

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each individual impurity in the portion of Methyl Salicylate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of salicylic acid or dimethyl 4-hydroxyisophthalate from the Sample solution

r_S = peak response of salicylic acid or dimethyl 4-hydroxyisophthalate from the Standard solution

C_S = concentration of USP Salicylic Acid RS or USP Methyl Salicylate Related Compound A RS in the Standard solution (µg/mL)

C_U = concentration of Methyl Salicylate in the Sample solution (µg/mL)

Acceptance criteria

Salicylic acid: NMT 0.1%

Dimethyl 4-hydroxyisophthalate: NMT 0.5%

5 SPECIFIC TESTS

5.1 SOLUBILITY IN 70% ALCOHOL

One volume of synthetic Methyl Salicylate dissolves in seven volumes of 70% alcohol. One volume of natural Methyl Salicylate dissolves in seven volumes of 70% alcohol, and the solution shows NMT a slight cloudiness.

5.2 SPECIFIC GRAVITY (841)

1.180-1.185 for the synthetic variety; 1.176-1.182 for the natural variety

Change to read:

5.3 OPTICAL ROTATION (781A), Procedures, Angular Rotation

[NOTE-This test is not required for synthetic Methyl Salicylate or that from Betula lenta.] (NF 1-DEC-2021)

Methyl Salicylate from Gaultheria procumbens is slightly levorotatory, with the angular rotation not exceeding -1.5° in a 100-mm tube.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers.

6.2 LABELING

Label it to indicate whether it was made synthetically or distilled from either of the plants of Gaultheria procumbens or Betula lenta.

6.3 USP REFERENCE STANDARDS (11)

USP Methyl Salicylate RS

USP Methyl Salicylate Related Compound A RS

Dimethyl 4-hydroxyisophthalate.

C₁₀H₁₀O₅ 210.18

USP Salicylic Acid RS